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      Dosimetric comparison of organs at risk using different contouring guidelines for definition of the clinical target volume in anal cancer

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          Abstract

          Background

          There are different contouring guidelines for definition of the clinical target volume (CTV) for intensity-modulated radiation therapy (IMRT) of anal cancer (AC). We conducted a planning comparison study to evaluate and compare the dose to relevant organs at risk (OARs) while using different CTV definitions.

          Methods

          Twelve patients with a primary diagnosis of anal cancer, who were treated with primary chemoradiation (CRT), were selected. We generated four guideline-specific CTVs and subsequently planned target volumes (PTVs) on the planning CT scan of each patient. An IMRT plan for volumetric arc therapy (VMAT) was set up for each PTV. Dose parameters of the planned target volume (PTV) and OARs were evaluated and compared, too.

          Results

          The mean volume of the four PTVs ranged from 2138 cc to 2433 cc. The target volumes contoured by the authors based on the recommendations of each group were similar in the pelvis, while they differed significantly in the inguinal region. There were no significant differences between the four target volumes with regard to the dose parameters of the cranially located OARs. Conversely, some dose parameters concerning the genitals and the skin varied significantly among the different guidelines.

          Conclusion

          The four contouring guidelines differ significantly concerning the inguinal region. In order to avoid inguinal recurrence and to protect relevant OARs, further investigations are needed to generate uniform standards for definition of the elective clinical target volume in the inguinal region.

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          Most cited references21

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          Use of normal tissue complication probability models in the clinic.

          The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) review summarizes the currently available three-dimensional dose/volume/outcome data to update and refine the normal tissue dose/volume tolerance guidelines provided by the classic Emami et al. paper published in 1991. A "clinician's view" on using the QUANTEC information in a responsible manner is presented along with a description of the most commonly used normal tissue complication probability (NTCP) models. A summary of organ-specific dose/volume/outcome data, based on the QUANTEC reviews, is included. Copyright 2010 Elsevier Inc. All rights reserved.
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            Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2×2 factorial trial

            Chemoradiation became the standard of care for anal cancer after the ACT I trial. However, only two-thirds of patients achieved local control, with 5-year survival of 50%; therefore, better treatments are needed. We investigated whether replacing mitomycin with cisplatin in chemoradiation improves response, and whether maintenance chemotherapy after chemoradiation improves survival. In this 2 × 2 factorial trial, we enrolled patients with histologically confirmed squamous-cell carcinoma of the anus without metastatic disease from 59 centres in the UK. Patients were randomly assigned to one of four groups, to receive either mitomycin (12 mg/m(2) on day 1) or cisplatin (60 mg/m(2) on days 1 and 29), with fluorouracil (1000 mg/m(2) per day on days 1-4 and 29-32) and radiotherapy (50.4 Gy in 28 daily fractions); with or without two courses of maintenance chemotherapy (fluorouracil and cisplatin at weeks 11 and 14). The random allocation was generated by computer and patients assigned by telephone. Randomisation was done by minimisation and stratified by tumour site, T and N stage, sex, age, and renal function. Neither patients nor investigators were masked to assignment. Primary endpoints were complete response at 26 weeks and acute toxic effects (for chemoradiation), and progression-free survival (for maintenance). The primary analyses were done by intention to treat. This study is registered at controlled-trials.com, number 26715889. We enrolled 940 patients: 472 were assigned to mitomycin, of whom 246 were assigned to no maintenance, 226 to maintenance; 468 were assigned to cisplatin, of whom 246 were assigned to no maintenance, 222 to maintenance. Median follow-up was 5.1 years (IQR 3.9-6.9). 391 of 432 (90.5%) patients in the mitomycin group versus 386 of 431 (89.6%) in the cisplatin group had a complete response at 26 weeks (difference -0.9%, 95% CI -4.9 to 3.1; p=0.64). Overall, toxic effects were similar in each group (334/472 [71%] for mitomycin vs 337/468 [72%] for cisplatin). The most common grade 3-4 toxic effects were skin (228/472 [48%] vs 222/468 [47%]), pain (122/472 [26%] vs 135/468 [29%]), haematological (124/472 [26%] vs 73/468 [16%]), and gastrointestinal (75/472 [16%] vs 85/468 [18%]). 3-year progression-free survival was 74% (95% CI 69-77; maintenance) versus 73% (95% CI 68-77; no maintenance; hazard ratio 0.95, 95% CI 0.75-1.21; p=0.70). The results of our trial--the largest in anal cancer to date--show that fluorouracil and mitomycin with 50.4 Gy radiotherapy in 28 daily fractions should remain standard practice in the UK. Cancer Research UK. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial.

              Chemoradiation as definitive therapy is the preferred primary therapy for patients with anal canal carcinoma; however, the 5-year disease-free survival rate from concurrent fluorouracil/mitomycin and radiation is only approximately 65%. To compare the efficacy of cisplatin-based (experimental) therapy vs mitomycin-based (standard) therapy in treatment of anal canal carcinoma. US Gastrointestinal Intergroup trial RTOG 98-11, a multicenter, phase 3, randomized controlled trial comparing treatment with fluorouracil plus mitomycin and radiotherapy vs treatment with fluorouracil plus cisplatin and radiotherapy in 682 patients with anal canal carcinoma enrolled between October 31, 1998, and June 27, 2005. Stratifications included sex, clinical nodal status, and tumor diameter. Participants were randomly assigned to 1 of 2 intervention groups: (1) the mitomycin-based group (n = 341), who received fluorouracil (1000 mg/m2 on days 1-4 and 29-32) plus mitomycin (10 mg/m2 on days 1 and 29) and radiotherapy (45-59 Gy) or (2) the cisplatin-based group (n = 341), who received fluorouracil (1000 mg/m2 on days 1-4, 29-32, 57-60, and 85-88) plus cisplatin (75 mg/m2 on days 1, 29, 57, and 85) and radiotherapy (45-59 Gy; start day = day 57). The primary end point was 5-year disease-free survival; secondary end points were overall survival and time to relapse. A total of 644 patients were assessable. The median follow-up for all patients was 2.51 years. Median age was 55 years, 69% were women, 27% had a tumor diameter greater than 5 cm, and 26% had clinically positive nodes. The 5-year disease-free survival rate was 60% (95% confidence interval [CI], 53%-67%) in the mitomycin-based group and 54% (95% CI, 46%-60%) in the cisplatin-based group (P = .17). The 5-year overall survival rate was 75% (95% CI, 67%-81%) in the mitomycin-based group and 70% (95% CI, 63%-76%) in the cisplatin-based group (P = .10). The 5-year local-regional recurrence and distant metastasis rates were 25% (95% CI, 20%-30%) and 15% (95% CI, 10%-20%), respectively, for mitomycin-based treatment and 33% (95% CI, 27%-40%) and 19% (95% CI, 14%-24%), respectively, for cisplatin-based treatment. The cumulative rate of colostomy was significantly better for mitomycin-based than cisplatin-based treatment (10% vs 19%; P = .02). Severe hematologic toxicity was worse with mitomycin-based treatment (P < .001). In this population of patients with anal canal carcinoma, cisplatin-based therapy failed to improve disease-free-survival compared with mitomycin-based therapy, but cisplatin-based therapy resulted in a significantly worse colostomy rate. These findings do not support the use of cisplatin in place of mitomycin in combination with fluorouracil and radiotherapy in the treatment of anal canal carcinoma. clinicaltrials.gov Identifier: NCT00003596.
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                Author and article information

                Contributors
                Hendrik-dapper@gmx.de
                Markus.Oechsner@mri.tum.de
                Stefan.Muench@mri.tum.de
                Christian.Diehl@mri.tum.de
                Jan.Peeken@tum.de
                Kai.Borm@mri.tum.de
                Stephanie.Combs@tum.de
                Journal
                Strahlenther Onkol
                Strahlenther Onkol
                Strahlentherapie Und Onkologie
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0179-7158
                1439-099X
                3 February 2020
                3 February 2020
                2020
                : 196
                : 4
                : 368-375
                Affiliations
                [1 ]GRID grid.6936.a, ISNI 0000000123222966, Department of Radiation Oncology, Klinikum rechts der Isar, , TU München, ; Ismaninger Str. 22, 81675 Munich, Germany
                [2 ]Partner Site Munich, Deutsches Konsortium für Translationale Krebsforschung (DKTK), Munich, Germany
                [3 ]GRID grid.4567.0, ISNI 0000 0004 0483 2525, Institute for Radiation Medicine (IRM), , Helmholtz Zentrum München, ; Ingolstädter Landstr. 1, Neuherberg, 85764 Germany
                Article
                1587
                10.1007/s00066-020-01587-y
                7089901
                32016496
                fd720d6d-75ea-420e-bc53-26ef1fda3e6b
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 1 December 2019
                : 16 January 2020
                Funding
                Funded by: Technische Universität München (1025)
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                Oncology & Radiotherapy
                anal cancer,contouring guidelines,organs at risk,dose distribution,inguinal lymph nodes

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